Clinical efficacy of laser therapy in the prevention of retinal detachment in patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis.

BACKGROUND: The aim of the present study was to evaluate the clinical efficacy of laser therapy in the prevention of retinal detachment in patients with acquired immunodeficiency syndrome (AIDS) and cytomegalovirus retinitis (CMVR). METHODS: A total of 96 eyes from 80 patients with AIDS and CMVR who received anticytomegalovirus (anti-CMV) treatment in the ophthalmology and infection centers of Beijing YouAn Hospital, between June 2016 and August 2018 were retrospectively investigated. The patients were randomly divided into a nonlaser group (50 eyes from 43 patients), who were treated with anti-CMV therapy, and a laser group (46 eyes from 37 patients), who were treated with a fundus laser method to close the retinopathy area after commencing the maintenance stage of anti-CMV treatment. Both groups were followed up for 24 months. The safety of laser therapy was observed, and the efficacy of the therapy was determined by evaluating the incidence of retinal detachment. RESULTS: The percentage of retinal detachment in the nonlaser group was 24% compared with 6.5% in the laser group (P=0.018). There was no significant difference between the two groups in the number of CD4+ T cells, the load of human immunodeficiency virus, or the time between the detachment and the end of the induction period. After laser therapy, 39.13% of patients exhibited keratic precipitates (KP), 30.43% had anterior chamber flare (±), 50% had anterior chamber flare (+), and 19.57% had anterior chamber flare (++). Intraocular pressure (IOP) increased in 3 eyes within 2 weeks of laser therapy. The retinal pigment reaction was not obvious in 8 eyes. CONCLUSIONS: The use of laser therapy in the main maintenance period of anti-CMV treatment can effectively reduce the incidence of retinal detachment in patients with AIDS and CMVR, and the therapy is safe and reliable.

Clinical Features of Ocular Pathology in Patients with Acquired Immunodeficiency Syndrome and Syphilis.

INTRODUCTION: The present study aimed to analyze the clinical features of ocular pathology in patients with acquired immunodeficiency syndrome (AIDS) combined with syphilis. METHODS: A total of 129 patients with AIDS and syphilis who first visited the Department of Ophthalmology in Beijing YouAn Hospital between 2012 and 2019 were included in the study. All patients underwent ophthalmologic examinations, such as best-corrected visual acuity (BCVA), slit lamp, intraocular pressure, dilated fundus examination, and color fundus photography as well as systemic examinations related to AIDS and syphilis. The patients were divided into four groups according to fundus disease: a normal fundi group, an HIV-related microvascular retinopathy (MVR) group, a cytomegalovirus retinitis (CMVR) group, and a syphilis-related retinopathy group. RESULTS: The incidence of fundus disease was 70.7%. There were 36 patients with normal fundi (29.3%), 40 with HIV-related MVR (31.0%), 25 with CMVR (19.4%) (including 11 cases of CMVR with syphilis-related retinopathy), 26 (20.2%) with syphilis-related retinopathy, 1 (0.78%) case with acute retinal necrosis, and 1 (0.78%) case with PORN. The median blood CD4 + T-cell count in the syphilis-associated retinopathy group was 357.5 cells/µl, which was significantly higher than in the other groups; this difference was statistically significant. In the CMVR group, 11 cases with concomitant syphilis-associated retinopathy had lower BCVA and 10 (90.9%) had active inflammatory manifestations in the anterior segment. CONCLUSION: The incidence of ocular pathology was high in patients co-infected with AIDS and syphilis, which might manifest in a variety of ocular manifestations; some patients may also have multiple ocular changes, which should be given great clinical attention.

Effect of Anti-CMV Therapy at Different Stages on Retinal Detachment in Patients with AIDS and CMVR.

INTRODUCTION: The present study aimed to investigate the effect of anti-cytomegalovirus (anti-CMV) therapy at different stages on retinal detachment in patients with acquired immunodeficiency syndrome (AIDS) and cytomegalovirus retinitis (CMVR). METHODS: Ninety-seven patients with AIDS and CMVR diagnosed and treated at the Ophthalmology and Infection Center of Beijing You'an Hospital, affiliated with Capital Medical University, from November 2017 to January 2020 were retrospectively analyzed. Of the 138 eyes included, 30 eyes with concomitant retinal detachment were enrolled as the study subjects. The eyes with retinal detachment were divided into a pre-induction group, an intra-induction group, and a post-induction group of anti-CMV therapy. The occurrence and characteristics of retinal detachment at different stages of anti-CMV therapy were observed. RESULTS: Retinal detachment occurred in 30 of the 138 eyes of 97 patients, with an incidence of retinal detachment of 21.74%. Retinal detachment occurred in eight eyes in the pre-induction group, with an incidence of 26.67%, and in four eyes in the intra-induction group, with an incidence of 13.33%. The difference in incidence between the two groups was statistically significant (P = 0.000). Retinal detachment occurred in 18 eyes in the post-induction group, with an incidence of 60%. The difference in incidence between the intra-induction group and the post-induction group was statistically significant (P = 0.001). CONCLUSION: The incidence of retinal detachment at the intra-induction stages of anti-CMV therapy was lower than that at the pre-induction stage, and retinal detachment during the anti-CMV therapy predominantly occurred after the end of the induction stage.

Effect of individualized therapy for AIDS patients with cytomegalovirus retinitis in intravitreal ganciclovir injections.

The effect of intravitreal ganciclovir injection combined with intravenous infusion on acquired immune deficiency syndrome (AIDS) patients with cytomegalovirus retinitis (CMVR) was investigated. A total of 32 eyes in 23 AIDS patients diagnosed as CMVR from 2017 to 2018 were included in the retrospective study. All patients underwent induction therapy by using intravenous drip of the anti-cytomegalovirus (CMV) agent ganciclovir (5 mg/kg q12h) combined with intravitreal ganciclovir injection (3 mg/time, 2 times/wk). The visual acuity, fundus photographs, lesion location, and number of intravitreal injections were observed preoperatively and postoperatively. Totally 14 eyes were cured during induction therapy. The number of injections [4.13 (2 to 6)] in CMVR patients with peripherally fundus lesions were significantly lower than those with central lesions [4.89 (2 to 6)]. The individualized therapy of intravitreal ganciclovir injections for AIDS patients with CMVR can effectively reduce the numbers of intravitreal injections.

A comparative study on retinal thickness of the macular region among AIDS patients with normal ocular fundus, HIV-related microvascular retinopathy patients, and cytomegalovirus retinitis patients.

The present study aims to measure the retinal thickness of the macular region of AIDS patients with normal ocular fundus, HIV-related microvascular retinopathy patients and cytomegalovirus retinitis (CMVR) patients by optical coherence tomography, and generalize the characteristics of retinal thickness of these 3 groups of patients.In this retrospective case series, the study object comprised of 111 AIDS patients who received diagnosis and treatment in the Ophthalmology Department of Beijing Youan Hospital. There are 33 patients in the AIDS normal ocular fundus group, 47 patients in the HIV-related microvascular retinopathy group, and 31 patients in the CMVR group. The retinal thickness of the macular region of these above patients was measured. The main indicators were retinal thickness of 9 macular partitions, best corrected visual acuity, CD4+ T lymphocyte count, and the start of highly active antiretroviral therapy.In the CMVR group, except for the nasal-outer and temporal-outer sectors, the thickness of the affected eye of the rest of the regions was greater than that of healthy eye (P < .05). Furthermore, there was a difference in thickness of the superior-outer and inferior-outer sectors between the AIDS normal ocular fundus group and HIV-related microvascular retinopathy group. The difference in thickness of the superior-inner sector between patients in the AIDS normal ocular fundus group and CMVR group was not statistically significant, while the difference in thickness of the rest of the regions was statistically significant. The difference in thickness of various regions between patients in the HIV-related microvascular retinopathy group and CMVR group was statistically significant.The retinal thickness of patients in the CMVR group generally increased, the retinal thickness of superior-outer and inferior-outer sections of patients in the HIV-related microvascular retinopathy group increased, when compared to the AIDS normal ocular fundus group. These optical coherence tomography (OCT) examination results present its own characteristics in different eye diseases in AIDS patients, and different stages of eye disease.

The Effects of Anti-LAP Monoclonal Antibody Down-regulation of CD4+LAP+ T Cells on Allogeneic Corneal Transplantation in Mice.

CD4+latency-associated peptide (LAP)+ T cells are a newly discovered T cell subset with suppressive function on immune responses. In this study, we investigate the role of CD4+LAP+ T cells on mice corneal allograft survival by down-regulating their expression using anti-LAP mAb. We show that a blockage of LAP leads to a decrease in the percentage of T cells expressing CD4+Foxp3+, CD4+GARP+, CD4+LAP+ and CD4+IL-10+ in the lymph nodes and spleens of mice undergoing orthotopic penetrating transplantation of corneal allograft, without affecting corneal graft survival. In addition, higher percentages of CD4+IFN-γ+ and CD4+IL-17A+ T cells in the lymph nodes and spleens, as well as TNF, IFN-γ, IL-17A and IL-6 levels in the aqueous humor, significantly increase in mice with rejected corneal grafts. The expression of TGF-ß1 decreases in corneal grafts during corneal rejection period. It is therefore possible that anti-LAP mAb can down-regulate the regulatory T cell subsets with its immunosuppressive effects. The rejection of corneal grafts seems to mainly be associated with the up-regulation of Th1 and Th17 cell subsets in peripheral lymph nodes.

The Balance of Th1/Th2 and LAP+Tregs/Th17 Cells Is Crucial for Graft Survival in Allogeneic Corneal Transplantation.

PURPOSE: CD4+LAP+ T cells are newly discovered regulatory T cells (Tregs). The aim of this study is to investigate the balance of Th1/Th2 and LAP+Tregs/Th17 in mice after allogeneic corneal transplantation. METHODS: A total of 65 mice received orthotopic penetrating transplantation. According to the survival scores of the grafts, the mice were divided into the rejection group and the survival group 3 weeks after transplantation. Th1, Th2, Th17, and regulatory T cells in the ipsilateral drainage lymph nodes and spleens were measured with flow cytometry. The related cytokines in aqueous humor were also analyzed. RESULTS: The frequencies of Foxp3+Tregs, GARP+Tregs, and LAP+Tregs in the survival group were significantly higher than those in the rejection group. And the expression trend of CD4+LAP+ T cells and CD4+GARP+ T cells was consistent. The level of IFN-γ, TNF, IL-6, and IL-17A markedly increased in aqueous humor during corneal allograft rejection. The ratio of Th1/Th2 and Th17/LAP+Tregs significantly increased in the rejection group at the 3rd week after corneal transplantation. CONCLUSION: LAP+Tregs might be regarded as substitute for Foxp3+Tregs. The balance of Th1/Th2 and LAP+Tregs/Th17 is crucial for corneal allograft survival.

Comparative analysis of cytomegalovirus retinitis and microvascular retinopathy in patients with acquired immunodeficiency syndrome.

AIM: To compare the clinical manifestation of cytomegalovirus (CMV) retinitis and microvascular retinopathy (MVR) in patients with acquired immunodeficiency syndrome (AIDS) in China. METHODS: A total of 93 consecutive patients with AIDS, including 41 cases of CMV retinitis and 52 cases of MVR were retrospectively reviewed. Highly active antiretroviral therapy (HAART) status was recorded. HIV and CMV immunoassay were also tested. CD4+ T-lymphocyte count and blood CMV-DNA test were performed in all patients. Aqueous humor CMV-DNA test was completed in 39 patients. Ophthalmological examinations including best corrected visual acuity (BCVA, by International Standard Vision Chart), intraocular pressure (IOP), slit-lamp biomicroscopy, indirect ophthalmoscopy were performed. RESULTS: In MVR group, the anterior segment examination was normal in all patients with a mean BCVA of 0.93±0.13. Blood CMV-DNA was 0 (0, 269 000) and 42 patients (80.77%) did not receive HAART. In CMV retinitis group, 13 patients (31.71%) had anterior segment abnormality. The mean BCVA was 0.64±0.35 and blood CMV-DNA was 3470 (0, 1 450 000). Nineteen patients (46.34%) had not received HAART. MVR group and CMV retinitis group the positive rates of aqueous CMV-DNA were 0 and 50%, respectively. Two patients with MVR progressed to CMV retinitis during the follow-up period. CONCLUSION: In comparison of CMV, patients with MVR have relatively mild visual function impairment. Careful ophthalmological examination and close follow-up are mandatory, especially for patients who have systemic complications, positive CMV-DNA test and without received HAART.

Fabrication of ultra-thin silicon nanowire arrays using ion beam assisted chemical etching.

Uniform dispersion of Au-Ag alloy nanoparticles underneath the surface of a Si wafer is realized via Au film pre-deposition and Ag ion implantation. The Au-Ag nanoparticles are used as catalysts in metal assisted chemical etching for fabricating Si nanowire arrays with average diameters of less than 10 nm. We find that the alloy catalysts introduced by ion implantation are the key to obtaining thin nanowire arrays and we also demonstrate that SiNWAs with various diameters could be simply produced by changing the thickness of the pre-deposited Au layer. Compared with the traditional process, ion beam assisted chemical etching is proven to be a convenient and efficient approach to fabricate ultra-thin SiNWAs on a large scale.

Aluminum citrate blocks toxicity of calcium oxalate crystals by preventing binding with cell membrane phospholipids.

BACKGROUND/AIMS: Renal damage from ethylene glycol and primary hyperoxaluria is linked to accumulation of calcium oxalate monohydrate (COM) crystals in the renal proximal tubule (PT). In vitro studies have shown that aluminum citrate (AC), uniquely among citrate salts, blocks COM cytotoxicity to tubular cells. These studies were designed to evaluate the interaction of COM with membrane phospholipids and the ability of AC to reduce COM toxicity by interfering with this interaction. METHODS: Interaction of COM with phospholipids was assessed using differential scanning calorimetric analysis of structural changes in specific liposomes. Interaction of COM with cell membranes was studied by measuring binding of radiolabeled crystals by human PT (HPT) cells. RESULTS: Analysis of liposomes prepared from phosphatidylserine (PS) or phosphatidylcholine (PC) showed that COM interfered with the gel-liquid transition of PS liposomes, but not that of PC liposomes. AC reversed the COM-induced changes in liposomal structure. AC inhibited the binding of [(14)C]-COM by HPT cells in a concentration-dependent manner. AC blocked COM binding by interacting with the crystal surface and not the cell membrane. CONCLUSION: These results indicate that AC blocks the binding of COM by PT cells, and consequently its cytotoxicity, by attaching to the surface of the crystal. Thus, AC, or a related compound that works by the same mechanism, could be a useful adjunct therapy to reduce the renal damage produced by severe hyperoxaluria.

Renal toxicity of ethylene glycol results from internalization of calcium oxalate crystals by proximal tubule cells.

Ethylene glycol exposure can lead to the development of renal failure due to the metabolic formation of calcium oxalate monohydrate (COM) crystals. The renal damage is closely linked to the degree of COM accumulation in the kidney and most likely results from a COM-induced injury to proximal tubule (PT) cells. The present studies have measured the binding and internalization of COM by primary cultures of normal PT cells from humans and from Wistar and Fischer-344 rats in order to examine the roles of these uptake processes in the resulting cytotoxicity. Internalization was determined by incubation of cells with [(14)C]-COM at 37 degrees C, removal of bound COM with an EDTA incubation, followed by solubilization of cells, as well as by transmission electron microscopy of COM-exposed cells. COM crystals were internalized by PT cells in time- and concentration-dependent manners. COM crystals were bound to and internalized by rat cells about five times more than by human cells. Binding and internalization values were similar between PT cells from Wistar and Fischer-344 rats, indicating that a differential uptake of COM does not explain the known strain difference in sensitivity to ethylene glycol renal toxicity. Internalization of COM correlated highly with the degree of cell death, which is greater in rat cells than in human cells. Thus, surface binding and internalization of COM by cells play critical roles in cytotoxicity and explain why rat cells are more sensitive to COM crystals. At the same level of COM accumulation after ethylene glycol exposure or hyperoxaluria in vivo, rats would be more susceptible than humans to COM-induced damage.

Calcium oxalate, and not other metabolites, is responsible for the renal toxicity of ethylene glycol.

Ethylene glycol (EG) is nephrotoxic due to its metabolism. Many studies suggest that the toxicity is due to oxalate accumulation, but others have conversely suggested that toxicity results from effects of metabolites such as glycolaldehyde or glyoxylic acid on proximal tubule cells. In vivo studies have indicated that accumulation of calcium oxalate monohydrate (COM) corresponds closely with development of toxicity in renal tissue. The present studies were therefore designed to clarify the roles of various metabolites in the mechanism for EG toxicity in vitro by comparing the relative cytotoxicity of EG metabolites using three measures of cell death, ethidium homodimer uptake, lactate dehydrogenase (LDH) release and the conversion of the tetrazolium salt XTT to a colorimetric dye. Human proximal tubule cells in culture were incubated in physiologic buffers for 6h at 37 degrees C with COM (147-735microg/ml, an oxalate equivalence of 1-5mM), glycolate (5-25mM), glyoxylate (0.2-5mM) and glycolaldehyde (0.2-2mM). To assess the effects of acidity on the cytotoxicity, incubations were carried out at pH 6-7.4. The results show that COM dose-dependently increased LDH release and ethidium homodimer uptake, while the other metabolites did not. Conversely, COM had no effect on the XTT assay, while high concentrations of glycolaldehyde and glyoxylate decreased XTT activity, but the latter only at acidic pH. The correlation between the uptake of ethidium homodimer and the release of LDH suggest that COM is cytotoxic to human kidney cells in culture, while the XTT assay does not validly measure cytotoxicity in this system. These results indicate that COM, and not glyoxylate or glycolaldehyde, is the toxic metabolite responsible for the acute tubular necrosis and renal failure that is observed in EG-poisoned patients.

Aluminum citrate inhibits cytotoxicity and aggregation of oxalate crystals.

Calcium oxalate monohydrate (COM), which represents a major component of kidney stones, is an end metabolite of ethylene glycol. COM accumulation has been linked with acute renal toxicity in ethylene glycol poisoning. COM injures the kidney either by directly producing cytotoxicity to the kidney cells or by aggregating in the kidney lumen leading to the blockage of urine flow. The present studies were designed to examine whether aluminum citrate could reduce the toxicity of COM. Toxicity was determined in human proximal tubule cells by leakage of lactate dehydrogenase or uptake of ethidium homodimer and in erythrocytes by degree of hemolysis. Aluminum citrate significantly inhibited the leakage of lactate dehydrogenase from human proximal tubule cells and protected against cell death from COM. The inhibitory effect of aluminum citrate was greater than that of other citrate or aluminum salts such as sodium citrate, aluminum chloride, calcium citrate, ammonium citrate or potassium citrate. Aluminum citrate significantly inhibited the aggregation of COM crystals in vitro and decreased red cell membrane damage from COM. Aluminum citrate appeared to directly interact with COM, but not with the cell membrane. As such, aluminum citrate reduced the cytotoxicity by a physico-chemical interaction with the COM surface, and not by dissolving the COM crystals. These studies suggest that aluminum citrate may protect against tissue damage that occurs with high levels of oxalate accumulation, especially in ethylene glycol poisoning and possibly in hyperoxaluric states.

The cytotoxicity of oxalate, metabolite of ethylene glycol, is due to calcium oxalate monohydrate formation.

Oxalate is a minor, but important metabolite of ethylene glycol and has been directly linked with acute and subchronic renal toxicity in ethylene glycol poisoning. Numerous studies have characterized the cytotoxicity of oxalate as including plasma membrane damage and organelle injury. Oxalate has two forms in vivo: oxalate ions and calcium oxalate monohydrate (COM) crystals that readily form in the presence of calcium. The present study was designed to compare the cytotoxicity of the oxalate ion and COM crystals in human and rat cells. In rat red blood cells, the oxalate ion did not increase hemolysis, while COM crystals produced hemolysis with a concentration-dependent increase. In human proximal tubule (HPT) cells in culture, COM suspensions, at concentrations >3 mM but with no oxalate ion, caused cytotoxicity as evidenced by the release of lactate dehydrogenase (LDH) into media. Cytotoxicity was not observed in HPT cells treated with oxalate solutions that contained no COM because EDTA prevented its formation. The cytotoxic effects of COM to HPT cells were potentiated by acidosis (pH 6.5), but not by glycolate, the major metabolite of ethylene glycol. The toxicity of COM to HPT cells and to proximal tubule cells from Wistar and F-344 rats, compared using both ethidium homodimer uptake and LDH leakage, increased in human and rat cells in a concentration-dependent manner. Rat cells were more sensitive to COM than HPT cells, but there were no apparent differences between the effects in Wistar cells and F-344 cells. These results demonstrate that COM crystals, and not the oxalate ion, are responsible for the membrane damage and cell death observed in normal human and rat PT cells and suggest that COM accumulation in the kidney is responsible for the renal toxicity associated with ethylene glycol exposure.